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FURIN furin, paired basic amino acid cleaving enzyme [ Homo sapiens (human) ]

Gene ID: 5045, updated on 5-Jan-2022

Summary

Official Symbol
FURINprovided by HGNC
Official Full Name
furin, paired basic amino acid cleaving enzymeprovided by HGNC
Primary source
HGNC:HGNC:8568
See related
Ensembl:ENSG00000140564 MIM:136950
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
FUR; PACE; SPC1; PCSK3
Summary
This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. Like other members of this convertase family, the product of this gene specifically cleaves substrates at single or paired basic residues. Some of its substrates include proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor. It is thought to be one of the proteases responsible for the activation of HIV envelope glycoproteins gp160 and gp140, and may play a role in tumor progression. Unlike SARS-CoV and other coronaviruses, the spike protein of SARS-CoV-2 is thought to be uniquely cleaved by this protease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2020]
Annotation information
Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in SARS-CoV-2 infection.
Expression
Ubiquitous expression in salivary gland (RPKM 50.5), liver (RPKM 36.0) and 25 other tissues See more
Orthologs
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Genomic context

See FURIN in Genome Data Viewer
Location:
15q26.1
Exon count:
20
Annotation release Status Assembly Chr Location
109.20211119 current GRCh38.p13 (GCF_000001405.39) 15 NC_000015.10 (90868588..90883457)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (91411818..91426687)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370969 Neighboring gene Sharpr-MPRA regulatory region 4312 Neighboring gene RNA, 7SL, cytoplasmic 363, pseudogene Neighboring gene Sharpr-MPRA regulatory regions 3826 and 8172 Neighboring gene FES proto-oncogene, tyrosine kinase Neighboring gene mannosidase alpha class 2A member 2

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Biological insights from 108 schizophrenia-associated genetic loci.
GeneReviews: Not available
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
GeneReviews: Not available

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of furin (paired basic amino acid cleaving enzyme) in human B cells PubMed
Envelope surface glycoprotein gp160, precursor env PAR1 inhibits the cleavage of HIV-1 gp160 to gp41 by furin PubMed
env Furin, a subtilisin-like eukaryotic endoprotease, is able to process HIV-1 gp160/gp140 to the cleavage products gp120 and gp41 at the cleavage site with the consensus amino acid sequence Arg-X-Lys/Arg-Arg PubMed
env Interaction between gp120 C5 region and gp41 disulfide loop in unprocessed HIV-1 Env glycoprotein is required for Env processing by furin PubMed
env V38M + N43T-N44K mutations impairs gPr160 cleavage by furin PubMed
Tat tat Furin cleaves HIV-1 Tat at amino acid residue 56, resulting in greatly reduced Tat transactivation activity PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables endopeptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
enables endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables endopeptidase activity TAS
Traceable Author Statement
more info
 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
 
enables nerve growth factor binding IDA
Inferred from Direct Assay
more info
PubMed 
enables peptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
enables peptide binding IDA
Inferred from Direct Assay
more info
PubMed 
enables protease binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables serine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables serine-type endopeptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
enables serine-type endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables serine-type endopeptidase activity TAS
Traceable Author Statement
more info
 
enables serine-type endopeptidase inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
involved_in amyloid fibril formation TAS
Traceable Author Statement
more info
 
involved_in blastocyst formation IEA
Inferred from Electronic Annotation
more info
 
involved_in collagen catabolic process TAS
Traceable Author Statement
more info
 
involved_in dibasic protein processing IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in extracellular matrix disassembly TAS
Traceable Author Statement
more info
 
involved_in extracellular matrix organization TAS
Traceable Author Statement
more info
 
involved_in negative regulation of endopeptidase activity IEA
Inferred from Electronic Annotation
more info
 
involved_in negative regulation of inflammatory response to antigenic stimulus TAS
Traceable Author Statement
more info
 
involved_in negative regulation of low-density lipoprotein particle receptor catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
NOT involved_in negative regulation of nerve growth factor production IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of transforming growth factor beta1 production IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in nerve growth factor production IDA
Inferred from Direct Assay
more info
PubMed 
involved_in peptide biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in peptide hormone processing IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in peptide hormone processing IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of membrane protein ectodomain proteolysis IC
Inferred by Curator
more info
PubMed 
involved_in positive regulation of transforming growth factor beta1 activation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein processing IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
acts_upstream_of_or_within protein processing IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein processing IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein processing IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in regulation of cholesterol transport IEA
Inferred from Electronic Annotation
more info
 
involved_in regulation of endopeptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of lipoprotein lipase activity TAS
Traceable Author Statement
more info
 
involved_in regulation of protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in regulation of signal transduction IEA
Inferred from Electronic Annotation
more info
 
involved_in secretion by cell IDA
Inferred from Direct Assay
more info
PubMed 
involved_in signal peptide processing IDA
Inferred from Direct Assay
more info
PubMed 
involved_in signal peptide processing TAS
Traceable Author Statement
more info
 
involved_in transforming growth factor beta receptor signaling pathway TAS
Traceable Author Statement
more info
 
involved_in viral life cycle IEP
Inferred from Expression Pattern
more info
PubMed 
involved_in viral protein processing TAS
Traceable Author Statement
more info
 
involved_in zymogen activation IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
located_in Golgi lumen TAS
Traceable Author Statement
more info
 
located_in Golgi membrane IMP
Inferred from Mutant Phenotype
more info
PubMed 
located_in Golgi membrane TAS
Traceable Author Statement
more info
 
located_in cell surface IDA
Inferred from Direct Assay
more info
PubMed 
located_in endoplasmic reticulum IGI
Inferred from Genetic Interaction
more info
PubMed 
located_in endosome membrane IEA
Inferred from Electronic Annotation
more info
 
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
 
NOT located_in extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in integral component of Golgi membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in membrane HDA PubMed 
is_active_in membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in membrane raft IDA
Inferred from Direct Assay
more info
PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
 
is_active_in trans-Golgi network IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in trans-Golgi network IDA
Inferred from Direct Assay
more info
PubMed 
located_in trans-Golgi network transport vesicle IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
furin
Names
FES upstream region
dibasic processing enzyme
furin, membrane associated receptor protein
paired basic amino acid residue-cleaving enzyme
proprotein convertase subtilisin/kexin 3
proprotein convertase subtilisin/kexin type 3
subtilisin-like proprotein convertase 1
NP_001276752.1
NP_001276753.1
NP_001369548.1
NP_001369549.1
NP_001369550.1
NP_001369551.1
NP_002560.1

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001289823.2NP_001276752.1  furin isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_001276752.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1, 2, and 3 encode the same protein.
    Source sequence(s)
    AC124248
    Consensus CDS
    CCDS10364.1
    UniProtKB/Swiss-Prot
    P09958
    UniProtKB/TrEMBL
    A0A024RC70
    Related
    ENSP00000484952.1, ENST00000610579.4
    Conserved Domains (4) summary
    cd04059
    Location:113402
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    smart00261
    Location:638675
    FU; Furin-like repeats
    pfam01483
    Location:484570
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:33107
    S8_pro-domain; Peptidase S8 pro-domain
  2. NM_001289824.2NP_001276753.1  furin isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_001276753.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1, 2, and 3 encode the same protein.
    Source sequence(s)
    AC124248
    Consensus CDS
    CCDS10364.1
    UniProtKB/Swiss-Prot
    P09958
    UniProtKB/TrEMBL
    A0A024RC70
    Related
    ENSP00000483552.1, ENST00000618099.4
    Conserved Domains (4) summary
    cd04059
    Location:113402
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    smart00261
    Location:638675
    FU; Furin-like repeats
    pfam01483
    Location:484570
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:33107
    S8_pro-domain; Peptidase S8 pro-domain
  3. NM_001382619.1NP_001369548.1  furin isoform 1 preproprotein

    Status: REVIEWED

    Source sequence(s)
    AC124248
    Conserved Domains (4) summary
    cd04059
    Location:113402
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    smart00261
    Location:638675
    FU; Furin-like repeats
    pfam01483
    Location:484570
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:33107
    S8_pro-domain; Peptidase S8 pro-domain
  4. NM_001382620.1NP_001369549.1  furin isoform 1 preproprotein

    Status: REVIEWED

    Source sequence(s)
    AC124248
    Related
    ENSP00000506143.1, ENST00000680053.1
    Conserved Domains (4) summary
    cd04059
    Location:113402
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    smart00261
    Location:638675
    FU; Furin-like repeats
    pfam01483
    Location:484570
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:33107
    S8_pro-domain; Peptidase S8 pro-domain
  5. NM_001382621.1NP_001369550.1  furin isoform 1 preproprotein

    Status: REVIEWED

    Source sequence(s)
    AC124248
    Conserved Domains (4) summary
    cd04059
    Location:113402
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    smart00261
    Location:638675
    FU; Furin-like repeats
    pfam01483
    Location:484570
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:33107
    S8_pro-domain; Peptidase S8 pro-domain
  6. NM_001382622.1NP_001369551.1  furin isoform 2 precursor

    Status: REVIEWED

    Source sequence(s)
    AC124248
    Conserved Domains (3) summary
    cd04059
    Location:113402
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    pfam01483
    Location:484570
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:33107
    S8_pro-domain; Peptidase S8 pro-domain
  7. NM_002569.4NP_002560.1  furin isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_002560.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript. Variants 1, 2, and 3 encode the same protein.
    Source sequence(s)
    AC124248, BC012181, BM043834, BP283962, X17094
    Consensus CDS
    CCDS10364.1
    UniProtKB/Swiss-Prot
    P09958
    UniProtKB/TrEMBL
    A0A024RC70
    Related
    ENSP00000268171.2, ENST00000268171.8
    Conserved Domains (4) summary
    cd04059
    Location:113402
    Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
    smart00261
    Location:638675
    FU; Furin-like repeats
    pfam01483
    Location:484570
    P_proprotein; Proprotein convertase P-domain
    pfam16470
    Location:33107
    S8_pro-domain; Peptidase S8 pro-domain

RNA

  1. NR_168464.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC124248
    Related
    ENST00000681804.1

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20211119

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p13 Primary Assembly

    Range
    90868588..90883457
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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